Mobilizing normal immune cells to the site of leukemia
Short summary of project: Development of a miniaturized model that reflects the patients’ bone marrow microenvironment at the time of leukemia by combining pre-clinical knowledge about leukemia in children (Den Boer group) and microfluidics nanotechnology (MIMETAS). The innovative bone marrow model will be used to investigate immune cell recruitment to the site of leukemia and modulation thereof, in order to find ways to improve patients’ responses to immunotherapy.
Relevance: Immunotherapy make use of patients’ own immune cells to kill cancer cells. Immunotherapy has the high potency to improve the outcome for children with leukemia by being more specific than current standard of care chemotherapies and by reducing its associated short and long-term side-effects. Leukemia originates in the bone marrow and recruiting more, and functional, immune cells to this site could improve the success rate of immunotherapy. However, although much is known about immune cell function, informative models are lacking to study how the recruitment and activity of immune cells can be stimulated at the time of leukemia.
Conceptualisation:
The Den Boer group discovered that leukemic cells induce a local microenvironment in the bone marrow, the so-called leukemia-educated niche, that impairs immune cell function and induces resistance to immunotherapy. The MIMETAS microfluidics system will be adapted to develop a new miniaturized model of this niche that allows live-imaging of immune cell migration dynamics and that simultaneously allows to quantify, characterize and modulate the function of recruited immune cells in eradicating leukemic cells in their niche.
Perspective: A well-characterized, reproducible and scalable bone marrow model can be used to investigate modulators of immune cell recruitment and activity at the time of leukemia. Such a model may further develop in predictive assays that indicate which patients may benefit from immunotherapy and/or need supplemental (immuno)modulating agents.